Table 1.
Drug profiles.
| Antifungal class | Polyene
|
Azoles
|
Echinocandins
|
Fluoropyrimidines | |||||
|---|---|---|---|---|---|---|---|---|---|
| Amphotericin B | Lipid formulations | Fluconazole | Itraconazole | Voriconazole | Posaconazole | Caspofungin | Anidulafungin | Flucytosine | |
| Formulation | intravenous | intravenous | intravenous/oral | intravenous/oral | intravenous/oral | oral | intravenous | intravenous | oral |
| Mechanism of action | Interaction with ergosterol, intercalation of fungal membrane, increased membrane permeability | Inhibition of cytochrome P450 14 alpha-demethylase, accumulation of lanosterol leading to perturbation of fungal cell membrane, fungistasis | Inhibition of cell-wall glucan synthesis leading to susceptibility of fungal cell to osmotic lysis | Interferance with DNA/RNA synthesis | |||||
| Loading dose/day | No | No | No | 400 mg iv /4 days 600 mg po /3 days | 12 mg/kg iv | No | 70 mg | 200 mg | No |
| Usual maintenance dose/day | 0.6–1.5 mg/kg | 3–6 mg/kg | 400–800 mg iv/po | 200 mg iv 400–600 mg po | 8 mg/kg iv 400 mg po | 600–800 mg | 50 mg | 100 mg | 100 mg/kg |
| Fequency of dosing | daily | daily | daily | twice daily | twice daily | 2–4 divided doses | daily | daily | every 6 hours |
| Half-life (hours) | 24 | 100–153 | 30 | 56–64 | dose dependent | 20 | 9–11 | 52 | 2.5–6 |
| Oral bioavailability | NA | NA | >90% | 55% | 96% | variable* | NA | NA | 75%–90% |
| CNS penetration | poor | data not available | very good | moderate | excellent | moderate | poor | poor | very good |
| Route of elimination | slow renal excretion | data not available | renal | fecal (primarily) renal | fecal | fecal (primarily) renal | fecal renal | fecal | renal |
| Dose reduction in renal failure | consider lipid formulation | not required | required | not required | not required | not required | not required | not required | required |
| Dose reduction in hepatic failure | data not available | data not available | not required | data not available | not recommended in severe cirrhosis | data not available | recommended for high Child-Pugh scores | not required | data not available |
| Major toxic effects | dose-limiting renal toxicity, fever, chills | less toxic than amphotericin B | well tolerated occasional GI intolerance | liver and GI toxicity | drug inter-actions, visual, liver, skin toxicity | well tolerated occasional GI and liver intolerance | well tolerated occasional histamine mediated symptoms | well tolerated occasional fever, diarrhea | GI intolerance marrow suppression |
Abbreviations: NA, not applicable; iv, intravenous; po, orally; CNS, central nervous system; GI, gastrointestinal.
* enhanced with food (2-fold), with high fat meal (4-fold)